rs2303191

Positions:

chr16-78164295-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016373.4(WWOX):c.516+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,612,444 control chromosomes in the GnomAD database, including 433,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43510 hom., cov: 31)

Exomes 𝑓: 0.73 ( 390295 hom. )

Consequence

WWOX
NM_016373.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0002358

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.92

Variant links:

Genes affected

WWOX (HGNC:12799): (WW domain containing oxidoreductase) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

WWOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-78164295-T-C is Benign according to our data. Variant chr16-78164295-T-C is described in ClinVar as [Benign]. Clinvar id is 260739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-78164295-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
WWOX	NM_016373.4 linkuse as main transcript	c.516+6T>C	splice_donor_region_variant, intron_variant	ENST00000566780.6
WWOX	NM_001291997.2 linkuse as main transcript	c.177+6T>C	splice_donor_region_variant, intron_variant
WWOX	NM_130791.5 linkuse as main transcript	c.516+6T>C	splice_donor_region_variant, intron_variant
WWOX	NR_120436.3 linkuse as main transcript	n.755+6T>C	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6 linkuse as main transcript	c.516+6T>C		splice_donor_region_variant, intron_variant		1	NM_016373.4	P1	Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.754

AC:

114579

AN:

151990

Hom.:

43457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.791

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.745

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.741

GnomAD3 exomes

AF:

0.748

AC:

185664

AN:

248274

Hom.:

69863

AF XY:

0.741

AC XY:

99764

AN XY:

134646

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.890

Gnomad SAS exome

AF:

0.723

Gnomad FIN exome

AF:

0.696

Gnomad NFE exome

AF:

0.717

Gnomad OTH exome

AF:

0.723

GnomAD4 exome

AF:

0.730

AC:

1065815

AN:

1460336

Hom.:

390295

Cov.:

AF XY:

0.728

AC XY:

528886

AN XY:

726428

show subpopulations

Gnomad4 AFR exome

AF:

0.803

Gnomad4 AMR exome

AF:

0.822

Gnomad4 ASJ exome

AF:

0.679

Gnomad4 EAS exome

AF:

0.906

Gnomad4 SAS exome

AF:

0.724

Gnomad4 FIN exome

AF:

0.694

Gnomad4 NFE exome

AF:

0.721

Gnomad4 OTH exome

AF:

0.730

GnomAD4 genome

AF:

0.754

AC:

114691

AN:

152108

Hom.:

43510

Cov.:

AF XY:

0.753

AC XY:

55990

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.799

Gnomad4 AMR

AF:

0.792

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.905

Gnomad4 SAS

AF:

0.745

Gnomad4 FIN

AF:

0.703

Gnomad4 NFE

AF:

0.722

Gnomad4 OTH

AF:

0.744

Alfa

AF:

0.730

Hom.:

17547

Bravo

AF:

0.764

Asia WGS

AF:

0.838

AC:

2915

AN:

3478

EpiCase

AF:

0.713

EpiControl

AF:

0.720

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 90. Only high quality variants are reported. -

Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 20, 2017

- -

Autosomal recessive spinocerebellar ataxia 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.046

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over